title: Anticancer potency of platinum(II) complexes containing both chloride anion and chelated carboxylate as leaving groups.
abstract: Three platinum complexes with both a chloride anion and a chelated carboxylate as leaving groups were synthesized and spectrally characterized. In vitro cytotoxicity of complexes 1-3 was evaluated against human A549, HCT-116, MCF-7, and HepG-2 tumor cell lines. The results showed that all the compounds exhibited effective cytotoxicity against the tested cell lines, nearly comparable to those of cisplatin and oxaliplatin. Notably, the activity of complex 2 was about 2-fold better than that of oxaliplatin against the HCT-116 cell line. Flow cytometry analysis indicated that these complexes produced death of tumor cells through an apoptotic pathway. The DNA-binding properties of the platinum-based compounds were also studied by agarose gel electrophoresis. The kinetics study showed that the chloride anion departs from the Pt atom quickly, whereas the five and/or six-membered ring formed by coordination of N,O-donors and the metal ion is opened a little more slowly by the rupture of a Pt-O bond, which helps us to further understand the mechanism of action of the newly synthesized complexes with biomolecules. Furthermore, the reaction rate constants of complexes 1-3 were roughly the same.
authors.affiliation: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gou
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Sun
authors.forename: Chuanzhu
authors.initials: C
authors.lastname: Gao
mesh_terms: D000838:Anions / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry* / Q000494:pharmacology*; D002712:Chlorides / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D017671:Platinum Compounds / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000838:Anions; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D002614:Chelating Agents; D002712:Chlorides; D017671:Platinum Compounds